Handschin, C. and Podvinec, M. and Amherd, R. and Looser, R. and Ourlin, J. -C. and Meyer, U. A.. (2002) Cholesterol and bile acids regulate xenosensor signaling in drug-mediated induction of cytochromes P450. Journal of Biological Chemistry, 277 (33). pp. 29561-29567.
|
PDF
- Published Version
298Kb |
Official URL: http://edoc.unibas.ch/dok/A5259316
Downloads: Statistics Overview
Abstract
Cytochromes P450 (CYP) constitute the major enzymatic system for metabolism of xenobiotics. Here we demonstrate that transcriptional activation of CYPs by the drug-sensing nuclear receptors pregnane X receptor, constitutive androstane receptor, and the chicken xenobiotic receptor (CXR) can be modulated by endogenous cholesterol and bile acids. Bile acids induce the chicken drug-activated CYP2H1 via CXR, whereas the hydroxylated metabolites of bile acids and oxysterols inhibit drug induction. The cholesterol-sensing liver X receptor competes with CXR, pregnane X receptor, or constitutive androstane receptor for regulation of drug-responsive enhancers from chicken CYP2H1, human CYP3A4, or human CYP2B6, respectively. Thus, not only cholesterol 7 alpha-hydroxylase (CYP7A1), but also drug-inducible CYPs, are diametrically affected by these receptors. Our findings reveal new insights into the increasingly complex network of nuclear receptors regulating lipid homeostasis and drug metabolism.
Faculties and Departments: | 03 Faculty of Medicine > Departement Biomedizin > Associated Research Groups > Pharmakologie (Handschin) 05 Faculty of Science > Departement Biozentrum > Growth & Development > Growth & Development (Handschin) 05 Faculty of Science > Departement Biozentrum > Services Biozentrum > Research IT (Podvinec) |
---|---|
UniBasel Contributors: | Handschin, Christoph and Podvinec, Michael |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
Publisher: | American Society for Biochemistry and Molecular Biology |
ISSN: | 0021-9258 |
e-ISSN: | 1083-351X |
Note: | Publication type according to Uni Basel Research Database: Journal article |
Language: | English |
Related URLs: | |
Identification Number: |
|
edoc DOI: | |
Last Modified: | 21 Nov 2017 12:55 |
Deposited On: | 22 Mar 2012 13:22 |
Repository Staff Only: item control page